Metastatic Castration-resistant Prostate CancerPhase 2PRO-XLNCT06568562
XL092 in Patients With Metastatic Castration-Resistant Prostate Cancer
A Phase 2 study testing XL092 in people with Metastatic Castration-resistant Prostate Cancer, run by University of Utah at 1 site in United States.
Trial summary
The purpose of this study is to determine how well the study drug XL092 is helping to treat a participant's cancer after 16 weeks of treatment. Researchers will also look at how safe the XL092 is and how well the XL092 is working. XL092 is an oral tablet that will be taken once a day. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- XL092
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2024to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant aged ≥ 18 years
- Disease criteria:
- --Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology
- Radiographic evidence of metatstatic disease
- Progression on or after prior treatment with 177Lu-PSMA-617 as determined by clinical investigator
- ECOG Performance Status ≤ 2.
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- Adequate organ function as defined as:
- Absolute neutrophil count ≥ 1500/mm3 .
- Platelet count ≥ 100,000/mm3 .
- Hemoglobin ≥ 9 g/dL .
- Total Bilirubin ≤ 1.5x institutional ULN. For subject's with Gilbert's disease, ≤ 3 x ULN.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. For subjects with CRPC and bone metastasis ALP ≤ 10 x ULN if predominantly bone-specific ALP.
- International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 upper limit of normal (ULN)
- Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault formula:
- ---Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)
- Urine protein-to-creatinine ratio (UPCR) ≤ 1.5 mg/mg (≤ 169.8 mg/mmol) creatinine or 24-hour urine protein <1.5 g.
- Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Section 5.4.1) during the course of the study and for 96 days after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm for the purpose of reproduction during these same periods.
- Must have recovered from adverse effects of any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy). CTCAE adverse events less than or equal to grade 1 are acceptable. CTCAE adverse events grade 2 or greater may be acceptable as determined by the Clinical Investigator.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Prior treatment with XL092
- Receipt of any type of small molecule kinase inhibitor, cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment.
- Note: Concomitant use of megestrol acetate, androgen-deprivation therapy and bone loss prevention treatment is permitted. Other types of hormonal therapies with similar use require prior approval from the Principal Investigator.
- Radiation therapy for bone metastasis or any other radiation therapy within 2 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- Note: Subjects with an incidental finding of an isolated brain lesion < 1 cm in diameter may be eligible after Principal Investigator approval if the lesion is radiographically stable for 4 weeks before first dose and does not require treatment per Investigator judgement.
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- Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
- -Concomitant anticoagulation with oral anticoagulants except for those specified below:-
- (a) Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose low molecular weight heparins (LMWH) or prophylactic dose of specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban
- (b) Therapeutic doses of LMWH or specified direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before enrollment and without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias [eg, ventricular flutter, ventricular fibrillation, Torsades de pointes (TdP)].
- Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant ischemic event within 6 months before first dose of study treatment.
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment.
- Note: Subjects with a diagnosis of DVT within 3 months are allowed if asymptomatic and stable at screening and treated with anticoagulation per standard of care before first dose of study treatment.
- Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.
- --Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
- Tumors invading the GI-tract from external viscera, tumors invading respiratory tracts
- Active peptic ulcer disease, inflammatory bowel disease including, ulcerative colitis or Crohn's disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis
- Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic
- Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
- Known gastric or esophageal varices
- Abdominal/peritoneal carcinomatosis
- Active perianal abscess
- History of pelvic or abdominal perforation
- History of bowel resection unless determined to be low risk of perforation by clinical investigator
- History of radiation therapy to the abdomen unless determined to be low risk of perforation by clinical investigator
- Prior GI surgery (particularly when associated with delayed or incomplete healing) unless completely healed and determined to be low risk of perforation by clinical investigator
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
- Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta.
- Note: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava) may be eligible following Principal Investigator approval.
- Other clinically significant disorders that would preclude safe study participation.
- Active infection requiring systemic treatment. Note: Prophylactic antibiotic treatment is allowed.
- Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- Known positive test for or suspected infection with clinically significant SARS-CoV-2 within one month before enrollment. Note: demonstration that the subject has fully recovered from the infection as determined by clinical investigator is required to be eligible for enrollment
- Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
- Malabsorption syndrome.
- Pharmacologically uncompensated, symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Requirement for hemodialysis or peritoneal dialysis.
- History of solid organ or allogeneic stem cell transplant.
- Major surgery (as defined in Appendix B; eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic nephrectomy within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 10 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.
- Note: Fresh tumor biopsies should be performed at least 7 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
- -Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms for males within 14 days per electrocardiogram (ECG) before first dose of study treatment.
- Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
- History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
- Inability to swallow tablets.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment requiring systemic treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
- Note: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial as approved by the Principal Investigator.
- Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.
- Participants taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112
Susan Sharry, 801-585-3453, susan.sharry@hci.utah.edu
About this study
Official title: PRO-XL: A Phase II Study of XL092 in Patients With Metastatic Castration-Resistant Prostate Cancer After Progression on Lutetium-177 (177Lu)-PSMA-617
The purpose of this study is to determine how well the study drug XL092 is helping to treat a participant's cancer after 16 weeks of treatment. Researchers will also look at how safe the XL092 is and how well the XL092 is working. XL092 is an oral tablet that will be taken once a day. Participants will return to clinic for regular visits for checkups and tests.
- Being tested
- XL092
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL092Drug
Also called Zanzalintinib
XL092 will be supplied as a tablet that will be taken at home once a day. XL092 tablets should not be crushed or chewed. Participants should drink a minimum of 8 ounces of water with each dose of XL092. Participants will be given enough XL092 to take at home for a full cycle.
| Study group | Role | What they receive |
|---|---|---|
| Treatment: All Patients | Experimental | XL092 is an oral tablet that will be taken once per day on a 28 day cycle. Participants will take a 60mg dose. Dose reductions to 40mg or 20mg may apply for in cases of dose interruption due to treatment-related toxicity. Receives: Drug: XL092 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with non-progressive disease after 16 weeks of treatment with XL092 as assessed by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1
To evaluate the disease control rate at 16 weeks in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with XL092 after progression on 177Lu-PSMA-617
Measured: 16 weeks
Secondary outcomes (7)
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type.
To evaluate the safety and tolerability of XL092 in the study population.
Measured: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 5.0).
To evaluate the safety and tolerability of XL092 in the study population.
Measured: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness.
To evaluate the safety and tolerability of XL092 in the study population.
Measured: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration.
To evaluate the safety and tolerability of XL092 in the study population.
Measured: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by relationship to study treatment.
To evaluate the safety and tolerability of XL092 in the study population.
Measured: 5 years
The proportion of patients achieving PSA decline of ≥ 50% compared to the baseline value prior to starting study treatment.
To evaluate the PSA 50% response rate in the study population.
Measured: 5 years
Overall survival (OS) as defined as the time from study drug initiation until death from any cause.
To evaluate OS in this study population.
Measured: 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2024
- Study start9 Dec 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis
- Responsible party
- Sponsor
- Investigators
- Umang Swami, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06568562
- Sponsor's protocol ID
- HCI178937
- Acronym
- PRO-XL
- Status last verified
- Jun 2026
- First submitted
- 21 Aug 2024
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRO-XL: A Phase II Study of XL092 in Patients With Metastatic Castration-Resistant Prostate Cancer After Progression on Lutetium-177 (177Lu)-PSMA-617
- ClinicalTrials.gov ID
- NCT06568562
- Acronym / sponsor ID
- PRO-XL / HCI178937
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Exelixis
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 23 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine how well the study drug XL092 is helping to treat a participant's cancer after 16 weeks of treatment. Researchers will also look at how safe the XL092 is and how well the XL092 is working. XL092 is an oral tablet that will be taken once a day. Participants will return to clinic for regular visits for checkups and tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment: All Patients | Experimental | Drug: XL092XL092 is an oral tablet that will be taken once per day on a 28 day cycle. Participants will take a 60mg dose. Dose reductions to 40mg or 20mg may apply for in cases of dose interruption due to treatment-related toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participant aged ≥ 18 years
- Disease criteria:
- --Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology
- ECOG Performance Status ≤ 2.
- Adequate organ function as defined as:
Key exclusion criteria (56 listed)
- Prior treatment with XL092
- Receipt of any type of small molecule kinase inhibitor, cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks or at least 5 half-lives, whichever shorter before first dose of study treatment.
- Note: Concomitant use of megestrol acetate, androgen-deprivation therapy and bone loss prevention treatment is permitted. Other types of hormonal therapies with similar use require prior approval from the Principal Investigator.
- Radiation therapy for bone metastasis or any other radiation therapy within 2 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XL092Also: ZanzalintinibXL092 will be supplied as a tablet that will be taken at home once a day. XL092 tablets should not be crushed or chewed. Participants should drink a minimum of 8 ounces of water with each dose of XL092. Participants will be given enough XL092 to take at home for a full cycle. | Drug | Treatment: All Patients |
Primary outcome
Proportion of participants with non-progressive disease after 16 weeks of treatment with XL092 as assessed by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1
Time frame: 16 weeks
To evaluate the disease control rate at 16 weeks in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with XL092 after progression on 177Lu-PSMA-617
7 secondary outcomes
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type.
Time frame: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by severity (as defined by the NIH CTCAE, version 5.0).
Time frame: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by seriousness.
Time frame: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by duration.
Time frame: 5 years
Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by relationship to study treatment.
Time frame: 5 years
The proportion of patients achieving PSA decline of ≥ 50% compared to the baseline value prior to starting study treatment.
Time frame: 5 years
Overall survival (OS) as defined as the time from study drug initiation until death from any cause.
Time frame: 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Metastatic Castration-resistant Prostate Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Umang Swami, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing XL092 in people with Metastatic Castration-resistant Prostate Cancer, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 56 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Susan Sharry (801-585-3453, susan.sharry@hci.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with non-progressive disease after 16 weeks of treatment with XL092 as assessed by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.